Bone Abstracts

Periostin is a matricellular protein expressed in late osteoblasts/osteocytes, which levels increase in response to PTH and mechanical loading. In turn periostin contributes to modeling based bone formation while restraining bone remodeling. Periostin is also a substrate of cathepsin K and inhibition of periostin blunts the effects of cathepsin K inhibition on bone. Considering the important role of osteocytes and their cathepsin K expression on osteolysis during lactation, we investigated the contribution of periostin to lactation-induced changes in bone microstructure.

12-week-old Postn^−/− and Postn^+/+ female mice were mated. After birth, lactating females were studied at day 14 of lactation (L), female mice of the same age were used as control (n=5–6 per group). Trabecular and cortical microarchitecture of the distal and midshaft femur was evaluated by a standard microCT (ScancoCT40) and porosity by a nanoCT (ScancoCT1172).

In Postn^+/+ mice, L significantly decreased periostin gene expression (−32% vs non-L, P<0.05) and increased cathepsin K, MMP13 and RANKL gene (+164, +138 and 213% vs non-L, all P<0.05). As expected, trabecular bone volume fraction (Tb. BV/TV), Tb. number (Tb.N), cortical bone volume (CtBV), Ct thickness (CtTh) decreased while Ct porosity increased in these conditions (−54, −15, −21, −33 and +14% respectively, vs non-L, P<0.05). In contrast, L had no effect on Tb. BV/TV, Tb.N, Ct.BV and porosity in Postn^−/− mice. CtTh decreased in response to L (−20% vs non-L, P<0.05) however significantly less in Postn^−/− compared to WT mice. Hence a significant interaction between periostin and lactation was found on these parameters (P<0.05).

These results indicate that inhibition of periostin expression during lactation, and potentially its degradation by cathepsin K from osteocytes, is an important mechanism for bone loss in these conditions. Whether periostin affects more remodeling and/ or osteocytic osteolysis is currently under investigation.